Dyslipidemia is a disruption in the amount of lipids in the blood. Dyslipidemia may be defined as any one of or a combination of (but not limited to) elevated low density lipoprotein cholesterol (LDL), elevated apolipoprotein B, elevated triglycerides (TGs), elevated lipoprotein(a), elevated apolipoprotein A, reduced high density lipoprotein cholesterol (HDL) or reduced apolipoprotein A1. Abnormal cholesterol and TG levels have been implicated in the onset of atherosclerosis, coronary artery disease, stroke and heart attacks. According to the NHANES III database 35% of men and 13% of women have low blood serum HDL cholesterol levels (defined as less than 40 mg/L). Various studies have shown that individuals with low HDL levels have a higher incidence of cardiovascular (CV) events than those with HDL levels greater than 65 mg/L. In the Framingham Heart Study, just under half (44%) of coronary events were observed in persons with HDL levels less than 40 mg/L (Castelli 1986). While cholesterol and TG levels can be mediated by lifestyle changes, some patients do not realize a significant enough reduction in overall cholesterol levels. To that effect, many patients supplement lifestyle changes with pharmaceutical agents to regulate cholesterol and TG levels.
Reduction of LDL cholesterol is currently the primary goal of dyslipidemia management. Along with clinically significant LDL cholesterol reductions, HMG CoA Reductase inhibitor (statin) therapy has morbidity and mortality benefit proven in more than 175,000 patient years of randomized data (Baigent. 2005).
The global antidyslipidemic market was worth $26.6 billion in 2007. The US accounted for 55% ($18.8 billion) with Japan, France, Germany, Italy, Spain and the UK together accounting for 23% of the market share. As expected, the market is dominated by statins which accounted for 61% of the US market share in 2007. The market shrank in 2007 following Zocor's loss of patent protection in the US. Further falls in revenue are expected in 2010 when the first generic versions of atorvastatin become available. The US dyslipidemic market is predicted to be worth $11.4 billion in 2017. However, this fall in revenue will predominantly impact the statin sub-section of the market. Sales of cholesterol uptake inhibitors e.g. ezetimibe, nicotinic acid and other dyslipidemic agents, such as probucol and benfluorex, accounted for almost $2.5 billion in sales in 2007 (which represented a 19% growth that year) and accounted for 13% of the US dyslipidemic sales. The compound annual growth rate (CAGR) for this class of drugs between 2004 and 2007 was 26% compared with −9% for statin therapy.
Approximately 1 in 2 statin treated patients in clinical practice do not reach their designated LDL goal. Furthermore, at least 1 in 10 patients in practice stop taking statin therapy because of side-effects (Avorn, Monette et al. 1998; Benner, Glynn et al. 2002; Jackevicius, Mamdani et al. 2002).
While statin therapy has been shown to be clinically effective in managing elevated LDL, it is less effective on reduced HDL, reduced apolipoprotein A1, elevated lipoprotein(a), elevated apolipoprotein A and elevated TGs. In the context of increases in the population prevalence of metabolic syndrome, particularly linked to non-LDL cholesterol dyslipidemia, there is considerable interest in optimizing dyslipidemia therapy using companion or add-on therapy. With intensifying competition in the market place and statin patent expires, there remains a need to develop novel therapies for the treatment of dyslipidemia and associated diseases.